TY - JOUR
T1 - Stromal-derived factor-1 in human tumors recruits and alters the function of plasmacytoid precursor dendritic cells
AU - Zoul, Weiping
AU - Machelon, Véronique
AU - Coulomb-L’Hermin, Aurore
AU - Borvakz, Jozef
AU - Nome, FranÇoise
AU - Isaeva, Tatyana
AU - Wei, Shuang
AU - Krzysieks, Roman
AU - Durand-Gasselin, Ingrid
AU - Gordon, Alan
AU - Pustilnik, Terri
AU - Curiel, David T.
AU - Galanaud, Pierre
AU - Capron, Frédérique
AU - Emilie, Dominique
AU - Curiel, Tyler J.
N1 - Funding Information:
Acknowledgments We thank O. Haller for antibody against MxA; A. Amara and F. Arenzana-Seisdedos for monoclonal antibody K15C against SDF-1; and S. Clayton, E. Kraus, S. Coquery, C. Chalouni and D. Olivares for technical assistance. T.J.C. was supported by grants from the NIH, the Baylor endowment and Golfers against Cancer. D.E., V.M. and P.G. were supported by the Association de Recherche sur le Cancer (ARC), France.
PY - 2001
Y1 - 2001
N2 - Dendritic-cell (DC) trafficking and function in tumors is poorly characterized, with studies confined to myeloid DCs (DC1s). Tumors inhibit DC1 migration and function, likely hindering specific immunity. The role of plasmacytoid Dcs (DC2s) in tumor immunity is unknown. We show here that malignant human ovarian epithelial tumor cells express very high levels of stromal-derived factor-1, which induces DC2 precursor (preDC2) chemotaxis and adhesion/transmigration, upregulates preDC2 very late antigen (VLA)-5, and protects preDC2s from tumor macrophage interleukin-10-induced apoptosis, all through CXC chemokine receptor-4. The VLA-5 ligand vascular-cell adhesion molecule-1 mediated preDC2 adhesion/transmigration. Tumor preDC2s induced significant T-cell interleukin-10 unrelated to preDC2 differentiation or activation state, and this contributed to poor T-cell activation. Myeloid precursor Dcs (preDC1s) were not detected. Tumors may weaken immunity by attracting preDC2s and protecting them from the harsh microenvironment, and by altering preDC1 distribution.
AB - Dendritic-cell (DC) trafficking and function in tumors is poorly characterized, with studies confined to myeloid DCs (DC1s). Tumors inhibit DC1 migration and function, likely hindering specific immunity. The role of plasmacytoid Dcs (DC2s) in tumor immunity is unknown. We show here that malignant human ovarian epithelial tumor cells express very high levels of stromal-derived factor-1, which induces DC2 precursor (preDC2) chemotaxis and adhesion/transmigration, upregulates preDC2 very late antigen (VLA)-5, and protects preDC2s from tumor macrophage interleukin-10-induced apoptosis, all through CXC chemokine receptor-4. The VLA-5 ligand vascular-cell adhesion molecule-1 mediated preDC2 adhesion/transmigration. Tumor preDC2s induced significant T-cell interleukin-10 unrelated to preDC2 differentiation or activation state, and this contributed to poor T-cell activation. Myeloid precursor Dcs (preDC1s) were not detected. Tumors may weaken immunity by attracting preDC2s and protecting them from the harsh microenvironment, and by altering preDC1 distribution.
UR - http://www.scopus.com/inward/record.url?scp=0035658072&partnerID=8YFLogxK
U2 - 10.1038/nm1201-1339
DO - 10.1038/nm1201-1339
M3 - Article
C2 - 11726975
AN - SCOPUS:0035658072
SN - 1078-8956
VL - 7
SP - 1339
EP - 1346
JO - Nature medicine
JF - Nature medicine
IS - 12
ER -